Assessment of cutaneous axon-reflex responses to evaluate functional integrity of autonomic small nerve fibers
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REVIEW ARTICLE
Assessment of cutaneous axon-reflex responses to evaluate functional integrity of autonomic small nerve fibers Mido M. Hijazi 1 & Sylvia J. Buchmann 2 & Annahita Sedghi 3 & Ben M. Illigens 4 & Heinz Reichmann 3 & Gabriele Schackert 1 & Timo Siepmann 3 Received: 22 September 2019 / Accepted: 11 February 2020 # The Author(s) 2020
Abstract Cutaneous autonomic small nerve fibers encompass unmyelinated C-fibers and thinly myelinated Aδ-fibers, which innervate dermal vessels (vasomotor fibers), sweat glands (sudomotor fibers), and hair follicles (pilomotor fibers). Analysis of their integrity can capture early pathology in autonomic neuropathies such as diabetic autonomic neuropathy or peripheral nerve inflammation due to infectious and autoimmune diseases. Furthermore, intraneural deposition of alpha-synuclein in synucleinopathies such as Parkinson’s disease can lead to small fiber damage. Research indicated that detection and quantitative analysis of small fiber pathology might facilitate early diagnosis and initiation of treatment. While autonomic neuropathies show substantial etiopathogenetic heterogeneity, they have in common impaired functional integrity of small nerve fibers. This impairment can be evaluated by quantitative analysis of axonal responses to iontophoretic application of adrenergic or cholinergic agonists to the skin. The axon-reflex can be elicited in cholinergic sudomotor fibers to induce sweating and in cholinergic vasomotor fibers to induce vasodilation. Currently, only few techniques are available to quantify axon-reflex responses, the majority of which is limited by technical demands or lack of validated analysis protocols. Function of vasomotor small fibers can be analyzed using laser Doppler flowmetry, laser Doppler imaging, and laser speckle contrast imaging. Sudomotor function can be assessed using quantitative sudomotor axon-reflex test, silicone imprints, and quantitative direct and indirect testing of sudomotor function. More recent advancements include analysis of piloerection (goose bumps) following stimulation of adrenergic small fibers using pilomotor axon-reflex test. We provide a review of the current literature on axon-reflex tests in cutaneous autonomic small fibers. Keywords Vasomotor . Sudomotor . Pilomotor . Axon-reflex . Autonomic
Introduction Autonomic small fibers mediate neural control of vital organs such as the cardiovascular, bronchopulmonary, gastrointestinal,
* Timo Siepmann [email protected] 1
Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr 74, 01307 Dresden, Germany
2
Department of Anaesthesiology, Operative Intensive Care Medicine and Pain Medicine, Vivantes Klinikum Spandau, Berlin, Germany
3
Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
4
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
and urogenital system as well as the skin. Autonomic
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